Biopolymers are key components of living organisms. The use of 252-Cf-plasma desorption mass spectrometry (252Cf-PDMS) to improve their characterization and detection and study chemical activity can have a significant impact on elucidating structure-function, early detection of disease and the question of biocompatibility of organic implants. One of the long term objectives of the proposed research is to develop 252Cf-PDMS to the level where it is routinely used for obtaining molecular weights of biomolecules in the molecular weight range from 1000-100,000 u with unit accuracy and pmol sensitivity. A second long term objective is to develop the use of modified surfaces for selective adsorption as a new dimension in analytical biomedical mass spectrometry. A third long term objective is to better utilize the fragmentation patterns inherent in the 252Cf-PD mass spectra of biopolymers to determine their sequence. An additional long term objective is to use 252Cf- PDMS to study plasma protein adsorption on biocompatible surfaces. One of the specific aims of the proposed research is to improve the current 252Cf-PD TOF technology for obtaining mass spectra of high molecular weight species. A second specific aim is to explore the use of different surfaces to selectively adsorb proteins and polyanionic biopolymers from aqueous solution in a manner that they can be readily desorbed as molecular ions in vacuum. A third specific aim is to develop a protocol for studying protein adsorption on different polymer substrates with the objective of addressing the question of biocompatibility. The experimental design and methods for accomplishing the first of the long range objectives and specific aims include the development of a new detector that will give enhanced sensitivity for high molecular weight ions, and the use of energy selection and pulsed fields for background reduction. For the utilization of surfaces for selective adsorption, four systems for surface modification will be studied. The first is based on the use of silanol chemistry on thin Si wafers. The second is based on surface modification of polyethylene terephthalate. The third is based on the electrochemical doping of electropolymerized poly-3-methyl- thiophene. For studying protein adsorption and biocompatibility, albumin and fibrinogen will be used as model plasma proteins. Thin films of different polymers will be prepared by spin casting and a combination of direct protein analysis and 252Cf-PDMS will be used to study the biocompatibility problem.